A gene-expression signature as a predictor of survival in breast cancer
New England Journal of Medicine 347, 1999-2009 (2002).
(Note: Current Rosetta Inpharmatics employees are shown in boldface type.)
Marc J van de Vijver¹ ‡, M.D., Ph.D., Yudong D He²‡, Ph.D.,
Laura J van ’t Veer¹ ‡, Ph.D., Hongyue Dai², Ph.D., Augustinus A M Hart¹, M.Sc.,
Dorien Voskui¹, Ph.D., George J Schreiber2, M.Sc., Johannes L Peters¹, M.D.,
Chris Roberts², Ph.D., Matthew J Marton², Ph.D., Mark Parrish²,
Douwe Atsma¹, Anke Witteveen¹, Annuska Glas¹, Ph.D., Leonie Delahaye¹,
Tony van der Velde¹, Harry Bartelink¹, M.D., Ph.D.,
Sjoerd Rodenhuis¹, M.D., Ph.D., Emiel Th Rutgers¹, M.D., Ph.D.,
Stephen Friend², M.D., Ph.D., and Rene Bernards¹ *, Ph.D.
Abstract
Background A more accurate means of prognostication in breast cancer will improve the selection of patients for adjuvant systemic therapy.
Methods Using microarray analysis to evaluate our previously established 70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I or II breast cancer and were younger than 53 years old; 151 had lymph-node–negative disease, and 144 had lymph-node–positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses.
Results Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (±SE) overall 10-year survival rates were 54.6±4.4 percent and 94.5±2.6 percent, respectively. At 10 years, the probability of remaining free of distant metastases was 50.6±4.5 percent in the group with a poor-prognosis signature and 85.2±4.3 percent in the group with a good-prognosis signature. The estimated hazard ratio for distant metastases in the group with a poor-prognosis signature, as compared with the group with the good-prognosis signature, was 5.1 (95 percent confidence interval, 2.9 to 9.0; P<0.001). This ratio remained significant when the groups were analyzed according to lymph-node status. Multivariable Cox regression analysis showed that the prognosis profile was a strong independent factor in predicting disease outcome.
Conclusions The gene-expression profile we studied is a more powerful predictor of the outcome of disease in young patients with breast cancer than standard systems based on clinical and histologic criteria.
¹ Divisions of Diagnostic Oncology, Radiotherapy and Molecular Carcinogenesis
and Center for Biomedical Genetics
The Netherlands Cancer Institute
121 Plesmanlaan
1066 CX Amsterdam
The Netherlands
² Rosetta Inpharmatics LLC*
12040 115th Avenue NE
Kirkland, Washington 98034
USA
‡ These authors contributed equally
* A wholly-owned subsidiary of Merck & Co., Inc.
# To whom correspondence should be addressed
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